The treatment of many diseases requires the growth of new blood vessels either in vivo or in vitro.
For example, during a heart attack the blood supply to a portion of the heart muscle is interrupted and the affected muscle dies or is injured. A goal of medical research is to develop methods to promote the growth of new blood vessels into, and around, the damaged heart tissue to aid its recovery.
Again by way of example, there is a continuing need for methods that promote the formation of blood vessels in vitro. These cultured blood vessels can be used to surgically repair or replace damaged blood vessels in an animal body. For example, cultured blood vessels can be used to repair blood vessel aneurisms.
Again by way of example, the implantation of a medical device into an animal body elicits a wound response. This type of wound response is called the foreign body response and results in the encapsulation of the implant by a poorly-vascularized, collagenous, capsule that can compromise the function of the implant. Formation of the collagenous capsule can be slowed or prevented by promoting the growth of blood vessels in the tissue surrounding the implanted device. There is, therefore, a continuing need for methods that promote the growth of blood vessels into the tissue surrounding implanted medical devices.
Large blood vessels, such as arteries and veins, include an endothelial lining surrounded by other tissue layers, such as a layer of muscle cells that regulate the diameter of the vessel, and thereby regulate blood pressure within the vessel. Some small blood vessels, such as capillaries, are made entirely from endothelial cells. The present invention provides methods for promoting endothelial morphogenesis, which is the formation of an animal anatomical structure from endothelial cells. Thus, the methods of the present invention can be used to promote the formation of new blood vessels, such as capillaries, that are composed entirely of endothelial cells; and also can be used to promote the formation of endothelial portions of blood vessels, such as promoting the formation of an endothelial lining in the lumen of an artificial blood vessel.
The present invention also provides implantable medical devices that promote endothelial morphogenesis, including the formation of new blood vessels, in the living tissue that completely, or partially, surrounds the device after implantation into an animal body. As described more fully herein, the methods and devices of the invention utilize osteoprotegerin protein, or biologically active fragments thereof, to promote endothelial morphogenesis.